Huff Alyssa, Karlen-Amarante Marlusa, Oliveira Luiz Marcelo, Ramirez Jan Marino
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, 98101.
Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA, 98108.
bioRxiv. 2024 Mar 13:2023.09.26.559560. doi: 10.1101/2023.09.26.559560.
Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder that results in multiple bouts of intermittent hypoxia. OSA has many neurologic and systemic comorbidities including dysphagia, or disordered swallow, and discoordination with breathing. However, the mechanism in which chronic intermittent hypoxia (CIH) causes dysphagia is unknown. Recently we showed the Postinspiratory complex (PiCo) acts as an interface between the swallow pattern generator (SPG) and the inspiratory rhythm generator, the preBötzinger Complex, to regulate proper swallow-breathing coordination (Huff et al., 2023). PiCo is characterized by interneurons co-expressing transporters for glutamate (Vglut2) and acetylcholine (ChAT). Here we show that optogenetic stimulation of ChATcre:Ai32, Vglut2cre:Ai32, and ChATcre:Vglut2FlpO:ChR2 mice exposed to CIH does not alter swallow-breathing coordination, but unexpectedly disrupts swallow behavior via triggering variable swallow motor patterns. This suggests, glutamatergic-cholinergic neurons in PiCo are not only critical for the regulation of swallow-breathing coordination, but also play an important role in the modulation of swallow motor patterning. Our study also suggests that swallow disruption, as seen in OSA, involves central nervous mechanisms interfering with swallow motor patterning and laryngeal activation. These findings are crucial for understanding the mechanisms underlying dysphagia, both in OSA and other breathing and neurological disorders.
阻塞性睡眠呼吸暂停（OSA）是一种常见的与睡眠相关的呼吸障碍，会导致多次间歇性缺氧发作。OSA有许多神经和全身合并症，包括吞咽困难或吞咽障碍，以及与呼吸的不协调。然而，慢性间歇性缺氧（CIH）导致吞咽困难的机制尚不清楚。最近我们发现，吸气后复合体（PiCo）作为吞咽模式发生器（SPG）和吸气节律发生器——前包钦格复合体之间的接口，来调节适当的吞咽-呼吸协调（Huff等人，2023年）。PiCo的特征是共表达谷氨酸转运体（Vglut2）和乙酰胆碱（ChAT）的中间神经元。在这里我们表明，对暴露于CIH的ChATcre:Ai32、Vglut2cre:Ai32和ChATcre:Vglut2FlpO:ChR2小鼠进行光遗传学刺激，不会改变吞咽-呼吸协调，但出乎意料地通过触发可变的吞咽运动模式破坏吞咽行为。这表明，PiCo中的谷氨酸能-胆碱能神经元不仅对吞咽-呼吸协调的调节至关重要，而且在吞咽运动模式的调制中也发挥重要作用。我们的研究还表明，如在OSA中所见的吞咽中断，涉及干扰吞咽运动模式和喉部激活的中枢神经机制。这些发现对于理解OSA以及其他呼吸和神经疾病中吞咽困难的潜在机制至关重要。
